UCLA Researchers Link Iron Accumulation To Alzheimer’s Disease

On the heels of a University of Rochester Medical Center (URMC) Department of Neurosurgery study which found that copper could factor into the onset and progression of the neurodegenerative condition, a second group of scientists has published research suggesting that iron accumulation could be one of the core contributing factors leading to the onset of the most common form of dementia.

Dr. George Bartzokis, a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA and senior author of the new study, and his colleagues examined two areas of the brain in patients with Alzheimer’s disease.

The researchers compared the hippocampus (a part of the brain known to be damaged early on in the disease’s progression) and the thalamus (which is typically affected only during the later stages of the disease) using brain-imaging techniques. They discovered iron levels had increased in the hippocampus and could be linked to tissue damage in that region. However, no such accumulation of the mineral was discovered in the thalamus, they report in the August edition of the Journal of Alzheimer’s Disease.

“While most Alzheimer’s researchers focus on the buildup of tau or beta-amyloid that results in the signature plaques associated with the disease, Bartzokis has long argued that the breakdown begins much further ‘upstream,’ UCLA explained Tuesday in a statement. “The destruction of myelin, the fatty tissue that coats nerve fibers in the brain, he says, disrupts communication between neurons and promotes the buildup of the plaques.”

Those amyloid plaques destroy and increase the amount of myelin, ultimately disrupting brain signals and potentially resulting in cell death and common clinical signs associated with Alzheimer’s. According to the researchers, myelin is produced by cells that are known as oligodendrocytes – cells which possess the highest levels of iron of any brain cell. While iron is essential for cellular function, the authors report too much of it can promote oxidative damage, and the brain is believed to be particularly vulnerable to this kind of damage.

In order to test their hypothesis elevated iron levels cause the tissue breakdown associated with Alzheimer’s, Bartzokis and his colleagues recruited 31 Alzheimer’s patients and 68 healthy control subjects. They then used an MRI technique capable of measuring the amount of brain iron in the protein ferritin to compare the amount of the element contained both in the hippocampus (which is involved in the formation of memories) and the thalamus.

“It is difficult to measure iron in tissue when the tissue is already damaged,” the senior author explained. “But the MRI technology we used in this study allowed us to determine that the increase in iron is occurring together with the tissue damage. We found that the amount of iron is increased in the hippocampus and is associated with tissue damage in patients with Alzheimer’s but not in the healthy older individuals – or in the thalamus. So the results suggest that iron accumulation may indeed contribute to the cause of Alzheimer’s disease.”

On Monday, the URMC study linking copper to the same neurodegenerative condition was published in the journal Proceedings of the National Academy of Sciences. According to the study authors, the mineral prevents the brain from clearing out toxic proteins, causing them to accumulate. When copper builds up in the brain, it can cause the blood brain barrier (which controls what enters and exists the brain) to break down. That causes amyloid beta, a toxic protein produced as a by-product of cellular activity, to accumulate.

“It is clear that, over time, copper’s cumulative effect is to impair the systems by which amyloid beta is removed from the brain,” lead author Rashid Deane, who is also a member of the Center for Translational Neuromedicine (CTN) explained in a statement. “This impairment is one of the key factors that cause the protein to accumulate in the brain and form the plaques that are the hallmark of Alzheimer’s disease.”